BioWorld Perspectives » Follow-on biologichttp://www.bioworld.com/perspectives
news, analysis, debates, commentary and camaraderie related to the development of biotechnology drugsThu, 30 Nov 2017 23:54:28 +0000en-UShourly1http://wordpress.org/?v=3.5It’s How You Look at the Vialhttp://www.bioworld.com/perspectives/2013/10/01/its-how-you-look-at-the-vial/
http://www.bioworld.com/perspectives/2013/10/01/its-how-you-look-at-the-vial/#commentsTue, 01 Oct 2013 16:07:10 +0000Mari Serebrovhttp://www.bioworld.com/perspectives/?p=1417What’s in a biosimilar name? That depends on whether the vial is half empty or half full. Seeing it as half full, many generic makers focus on the similarities between a follow-on and its reference biologic. Because of those similarities,...

]]>What’s in a biosimilar name? That depends on whether the vial is half empty or half full.

Seeing it as half full, many generic makers focus on the similarities between a follow-on and its reference biologic. Because of those similarities, they say biosimilars and their reference product should share the same international nonproprietary name (INN) – as is the practice with traditional generic drugs. That’s the argument the Generic Pharmaceutical Association (GPhA) made in the citizen petition it submitted to the FDA earlier this month.

Used to cashing in on the success of a small molecule brand drug by sharing its INN and through automatic substitution with little marketing effort, generic makers frame their argument as one of access to cheaper biologics. The more biosimilars are seen as the same as the innovator drug, the easier their job will be in selling them to the market at discounted prices.

On the other side of the debate are brand makers, joined by several patient advocates, who see the vial as half empty. In demanding unique names for each biosimilar, they highlight the differences between biosimilars and the innovator biologic.

Used to having a corner on the biologic market, the innovators, some of whom are developing their own biosimilars, frame the argument as one of safety. The more patients and prescribers are aware of the differences and exactly which version of a drug is being dispensed, the easier it will be to track adverse events – and perhaps maintain the innovator’s marketing edge.

Either way, the truth is likely found somewhere in the middle of the vial.

As with all follow-on, generic and me-too drugs, there are both similarities and differences. But given the complexity of some biologics, there are questions patients will want answered before they trust their health to a new version of a biologic that’s working for them. Exactly how similar is the “highly similar” standard set by the FDA for biosimilars? Is it simply a matter of “we’ll know it when we see it”?

And given the potential differences, no matter how slight, the FDA’s stance that biosimilars don’t need to demonstrate safety also raises a few questions. What is the certainty that minor manufacturing differences won’t become a major clinical difference in a subset of patients, especially if the mechanism of the innovator biologic isn’t fully understood? Short of massive clinical trials, how can drugmakers demonstrate that those differences are truly minor? And, contrary to the FDA’s current position, should biosimilar makers have to demonstrate the safety of their products?

Patients don’t care if the vial is half full or half empty. They want to know that the biologic they’re given is as safe and effective as the one they’ve used before.

]]>http://www.bioworld.com/perspectives/2013/10/01/its-how-you-look-at-the-vial/feed/0Omontys Recall Rings Alarm Over Biosimilarshttp://www.bioworld.com/perspectives/2013/02/27/omontys-recall-rings-alarm-over-biosimilars/
http://www.bioworld.com/perspectives/2013/02/27/omontys-recall-rings-alarm-over-biosimilars/#commentsWed, 27 Feb 2013 14:00:11 +0000Mari Serebrovhttp://www.bioworld.com/perspectives/?p=1293Despite what the New York Times and its echoers have said, makers of innovative biologics have legitimate reason to sound alarms about automatic substitution of biosimilars that have not proven their interchangeability – and it’s not just because of the...

]]>Despite what the New York Times and its echoers have said, makers of innovative biologics have legitimate reason to sound alarms about automatic substitution of biosimilars that have not proven their interchangeability – and it’s not just because of the potential impact to their bottom line. That point was driven home by the recent recall of Affymax Inc. and Takeda Pharmaceutical Co. Ltd.’s Omontys (peginesatide).

Although Omontys is not a biosimilar, the unexpected postmarketing reports of serious hypersensitivity reactions linked to the erythropoiesis-stimulating agent (ESA) served as a reminder of the variability of biologics, their sensitivity to minute manufacturing changes and the difficulty of catching a rare safety signal in the full-blown biologic development process – let alone an abbreviated biosimilar path. It also evoked memories of a similar incident a number of years ago in which an increase in pure red-cell aplasia linked to Eprex, another ESA, was attributed to a change in rubber stoppers in the drug vials.

Both incidents should give the FDA pause about its approach to biosimilar approval. Because of the variability of biologics, biotechs and patient advocacy groups have urged the agency to require safety data for biosimilars. While the agency maintains that patient safety is its primary concern with any drug, it insists that since the reference biologic has demonstrated safety and efficacy, all a biosimilar must do is demonstrate similarity to the reference drug. The goal is not to require redundant clinical trials that would be expensive, unnecessary and unethical, according to the agency.

In light of the Omontys and Eprex recalls, the FDA, at the least, should require that marketed biologics and biosimilars have packaging identical to that used in clinical trials and be manufactured at the same facility, under the same processes, as that of the trial drug.

Neither the FDA nor most biotechs want the biosimilar path to fail. But they understand the complexities of making biologics, and they know that one disaster now could doom or indefinitely delay the new approval path.

Unfortunately, people not so familiar with the differences between biologics and small molecule drugs, which are far less complex than biologics, too often equate biosimilars with generics. Since generics are unquestionably accepted as equivalent to small molecule reference drugs, they can be substituted automatically for the brand drug at the pharmacy. Thus, they account for about 80 percent of the prescription drugs dispensed in the U.S. Many generics advocates envision the same success for biosimilars – if the FDA would just start approving them.

Yet even generics have had equivalency problems. Last year, the FDA found that a generic bupropion, approved based on extrapolated data, wasn’t comparable to GlaxoSmithKline plc’s antidepressant Wellbutrin XL 300 mg (bupropion). That incident raised questions about the use of extrapolated data for both generics and biosimilars.

Other generic equivalency issues were raised last year in a Government Accountability Office (GAO) report, which questioned the substitution of generics for some indications. The GAO cited a study that found patients on selective serotonin reuptake inhibitors (SSRIs) who switched to cheaper substitutes mid-treatment averaged $881 more in total health care costs than those who stayed on the more expensive brand SSRI due to a higher rate of hospitalizations and emergency room visits.

Another study referenced in the GAO report looked at the annual health care costs for kidney transplant patients treated with narrow therapeutic index immunosuppressants. Researchers found that patients on the generic needed higher doses of the drug or an additional immunosuppressant to maintain their new kidneys as compared with those on the brand drug.

Such issues could be magnified for biosimilars, given all that scientists don’t know yet about biologics. That, coupled with the public’s tendency to consider biosimilars as just more generics, should set off other alarms for makers of reference biologics. Some courts – most recently, the Alabama Supreme Court – have held brand drugmakers liable for adverse events caused by generics, which share the same labeling as the brand drug. Recognizing all that can go wrong in the manufacture of a biologic, makers of a reference biologic don’t want to be on the legal hook for a biosimilar that a judge or jury mistakenly equates with a generic.

]]>http://www.bioworld.com/perspectives/2013/02/27/omontys-recall-rings-alarm-over-biosimilars/feed/0Biosimilars are Changing the Global Gamehttp://www.bioworld.com/perspectives/2013/01/23/biosimilars-are-changing-the-global-game/
http://www.bioworld.com/perspectives/2013/01/23/biosimilars-are-changing-the-global-game/#commentsWed, 23 Jan 2013 15:01:09 +0000Mari Serebrovhttp://www.bioworld.com/perspectives/?p=1252I recently took a few months off from daily deadlines to explore the evolving world of biosimilars for the newest BioWorld Data report, The Biosimilars Game: A Scorecard for Opportunities, Threats and Critical Strategies. It was quite an eye-opening adventure....

Even though I’ve been covering biosimilars for BioWorld for a few years now, I was surprised at the impact these follow-on biologics (FOBs) are having throughout the world, given that the European Union (EU) is continuing its two-year approval slump and no biosimilar candidates have stepped up to bat yet in Canada or the U.S.

Some of my surprise undoubtedly stems from a lifetime of watching the home teams play. With that caveat in mind, I’ll share a few of the stats that had me doing a bit of a double-take:

The number of EU and U.S. clinical trials for biosimilars being conducted by foreign companies that have never played in highly regulated markets before;

That Malaysia adopted a biosimilar regulatory path, based on that of the EU, a year before the World Health Organization released its guidelines and nearly two years before Congress cleared the way for a U.S. path. But countries like China, Israel and Russia have yet to draft a biosimilar rulebook;

That Australia, Brazil, Japan, Malaysia and South Korea have all approved at least one official biosimilar, while the FDA is still waiting for its first application. In all fairness, most of these countries had their regulatory path in place at least a year before the FDA had the authority to lay out its ground rules. However, Brazil, which has approved two biosimilars since 2010, got into the game the same year as the FDA;

The emergence of the MENA region (the Middle East and North Africa) as a growing market for biosimilars and other drugs;

That Cuba is a major dealmaker and biosimilar partner in several emerging markets;

The diversity of the players, especially since some of the most ambitious ones on the global field are not the major league biopharma teams. For instance, Geneva-based BioXpress Therapeutics SA is working on a pipeline of 18 biosimilars, including 16 monoclonal antibodies (MAbs), and Sapporo, Japan’s Gene Techno Science Co. Ltd. has nine biosimilars in development, including six MAbs, plus a biosimilar filgrastim awaiting Japanese approval;

The position biosimilars and other FOBs play in helping many emerging markets break into the biologics field. That’s especially true in South Korea, which is looking to become a world leader in biosimilar development. Thanks to a package of financial and institutional aids for biologic testing and production facilities it provided a few years ago, the South Korean government expects that, by 2015, the country’s new biosimilar sector will have created 120,000 jobs, contributed $2 billion to the gross domestic product and generated $1 billion in exports. By 2020, South Korea predicts biosimilars made in that country will account for more than one-fifth of the global market.

Another statistic that caught my attention is the sheer number of biosimilars being developed worldwide. As of December, the FDA had received 50 requests for initial biosimilar discussion meetings, referencing a total of 12 biologics. But globally, more than 276 biosimilars are in the pipeline, referencing 19 MAbs, as well as other biologics such as epoetin, etanercept, filgrastim, insulin and interferon. (That’s not counting all the companies that haven’t fully disclosed their pipelines.)

In other words, while biosimilars may still be in the sandlot in the U.S., they’re already headed toward a world series elsewhere.